Clinical phenotype in infants with negative Zika virus immunoglobulin M testing born to mothers with confirmed Zika virus infection during pregnancy

Abstract

Background Recommended testing for both infants with Zika‐associated birth defects (i.e., microcephaly and selected brain or eye anomalies) and infants without birth defects whose mothers had laboratory evidence of possible Zika virus (ZIKV) infection during pregnancy includes nucleic acid amplification testing (NAAT) and immunoglobulin M (IgM) testing within days after birth. Brain and eye defects highly specific for congenital ZIKV infection have been described; sporadic reports have documented negative ZIKV testing in such infants. Methods Infants from the U.S. Zika Pregnancy and Infant Registry and Zika Birth Defects Surveillance with Zika‐associated birth defects and maternal and infant laboratory testing for ZIKV and two congenital infections (i.e., cytomegalovirus [CMV] and toxoplasmosis) were reviewed for phenotype and laboratory results. Infants with at least one defect considered highly specific for congenital ZIKV infection were designated as having congenital Zika syndrome (CZS) clinical phenotype for this study. Results Of 325 liveborn infants with Zika‐associated birth defects and laboratory evidence of maternal ZIKV infection, 33 (10%) had CZS clinical phenotype; 172 (53%) had ZIKV IgM testing with negative or no ZIKV NAAT. ZIKV IgM was negative in the remaining 121 infants, and for 90%, testing for CMV and toxoplasmosis was missing/incomplete. Among 11 infants testing negative for ZIKV IgM, CMV, and toxoplasmosis, 2 infants had CZS clinical phenotype. Conclusions These data add support to previous reports of negative ZIKV IgM testing in infants with clear maternal and phenotypic evidence of congenital ZIKV infection. Follow‐up care consistent with the diagnosis is recommended regardless of infant ZIKV test results.

Zika virus as a cause of birth defects: Were the teratogenic effects of Zika virus missed for decades?

“…Of note, both women had returned to the United States after giving birth; thus, subsequent exposure to ZIKV was unlikely. Both children were negative for ZIKV antibodies when tested at six and eight years old; however, ZIKV antibodies are not always present in children who were infected in utero (Adebanjo et al, 2017; Godfred‐Cato et al, 2021). Several genetic alterations have been associated with a CZS‐like phenotype but the findings in these two cases reported were inconsistent with these disorders (Chu et al, 2018).…”